What is pseudohyponatremia?

Pseudohyponatremia: Definition, Causes, and Management

Pseudohyponatremia is an artifactual decrease in measured serum sodium concentration that does not reflect true sodium concentration in the blood and does not cause clinical symptoms of hyponatremia. It occurs when laboratory methods using indirect ion-selective electrodes (ISE) measure falsely low sodium levels in the presence of elevated serum proteins or lipids 1.

Mechanism of Pseudohyponatremia

• Pseudohyponatremia occurs due to laboratory measurement artifacts rather than actual sodium deficiency 2
• It happens primarily when sodium is measured using indirect ion-selective electrode (ISE) methods that require sample dilution before measurement 1
• In normal serum, water constitutes approximately 93% of serum volume, with proteins and lipids making up the remaining 7% 1
• When lipids or proteins are significantly elevated, they occupy a larger proportion of serum volume, reducing the water fraction 3
• Since sodium exists only in the water phase of serum, indirect ISE methods that measure sodium concentration in the total serum volume (including lipids and proteins) report falsely low values 1

Common Causes of Pseudohyponatremia

• Severe hyperlipidemia (elevated triglycerides) 4
• Hyperproteinemia (multiple myeloma, Waldenstrom macroglobulinemia) 2
• Hyperglycemia (can cause both true dilutional hyponatremia and pseudohyponatremia) 2
• Paraproteinemias 1
• Use of intravenous immunoglobulin therapy 1

Distinguishing Pseudohyponatremia from True Hyponatremia

• Pseudohyponatremia has normal serum osmolality (275-290 mOsm/kg), while true hyponatremia has low osmolality 5
• Patients with pseudohyponatremia do not develop symptoms of hyponatremia (headache, nausea, confusion, seizures) 1
• Direct ISE methods (used in blood gas analyzers) provide accurate sodium measurements even in the presence of hyperlipidemia or hyperproteinemia 6
• The difference between sodium measured by indirect ISE and direct ISE methods increases with rising lipid levels 6

Diagnostic Approach

• Check serum osmolality - normal in pseudohyponatremia, low in true hyponatremia 5
• Measure lipid profile, particularly triglycerides 4
• Check serum protein levels and screen for paraproteins if indicated 2
• Compare sodium measurements using both direct ISE (blood gas analyzer) and indirect ISE methods - significant differences suggest pseudohyponatremia 1
• Consider ultracentrifugation of hyperlipidemic samples to clear excess lipids before sodium measurement 6

Clinical Implications

• Pseudohyponatremia does not require sodium correction therapy as the actual sodium concentration in the blood water phase is normal 1
• Attempting to correct pseudohyponatremia with hypertonic saline can lead to dangerous hypernatremia 2
• The underlying cause (hyperlipidemia, hyperproteinemia) should be addressed instead 4
• Laboratories should consider reflexing to direct ISE methods when lipemic index exceeds 700 on Roche Cobas 8000® analyzers 6

Common Pitfalls to Avoid

• Treating pseudohyponatremia as true hyponatremia can lead to iatrogenic hypernatremia and its complications 1
• Relying solely on indirect ISE methods in patients with known or suspected hyperlipidemia or hyperproteinemia 6
• Using Intralipid®-based lipemia cutoffs, which do not accurately reflect the interference seen in true hyperlipidemic samples 6
• Failing to investigate the underlying cause of elevated lipids or proteins 4
• Not communicating with the laboratory about the measurement method used when interpreting sodium values in patients with potential pseudohyponatremia 3

In summary, pseudohyponatremia represents a laboratory artifact rather than a true electrolyte disorder. Recognizing this condition is crucial to avoid unnecessary and potentially harmful sodium correction therapies. The focus should be on identifying and treating the underlying cause of elevated serum lipids or proteins.